tbuckley/cabot-search huggingface dataset:
Comparative effectiveness of abiraterone and enzalutamide in the first-line treatment of metastatic castration-resistant prostate cancer (mCRPC): A retrospective cohort study in a large database of deeply curated EHR real-world data (RWD) from community oncology practices in the US.
Authors: Huijun An, Martin W. Schoen, Jennifer Rider, Anna E. Schorer, Jessica Ken, Li Chen, Amy Alabaster, Yanina Natanzon
Journal: Journal of Clinical Oncology (2023)

175 Background: Abiraterone(A) and enzalutamide(E), both oral androgen receptor targeted agents, are available as first-line treatment options for mCRPC patients. Direct comparisons of efficacy have not been performed for mCRPC patients primarily receiving their cancer care outside of academic centers or integrated health care systems. The study aims to evaluate the real-world effectiveness between first-line A and E-containing regimens in mCRPC patients primarily receiving care in the US community oncology setting. Methods: Patients were selected from ConcertAI Patient 360 Prostate data product, a large de-identified database of deeply curated EHR RWD, sourced from data sharing agreements with community oncology practices. mCRPC patients treated with a first-line A or E-cont. regimen between 1/2011 and 6/2022 were included. OS, TTNT, TTD outcomes were described using KM estimates and evaluated with Cox proportional hazard (HR) model. Confounding was addressed with inverse probability treatment weighting (IPTW) propensity scores based on age, BMI, ECOG, prior anti-androgen exposure, smoking status, comorbidities, and nadir PSA. Sensitivity analysis evaluated KM and HR for each covariate strata. Hazard ratios were also evaluated with multiple imputation by chained equations for missing covariates. Results: From 3,578 mCRPC patients, 1,210 (33.8%) received E-cont. regimen and 1,357 (37.9%) received A-cont. regimen(ref) with a median of 8 months duration for both drugs. Adjusted HR (aHR) for all three outcomes showed a slight increase in effectiveness for E albeit not significant (OS (aHR 0.99, CI 0.87-1.12), TTNT (aHR 0.98, CI 0.89-1.08). Adjusted model including imputation (iHR) supported unimputed results (OS (iHR 0.97, CI 0.88-1.07), TTNT (aHR 0.94, CI 0.9-1.10). The HRs for OS, TTNT and TTD in sicker patients were consistent (2+ ECOG TTNT (aHR 0.95, 0.81-1.12)), (BMI &gt;30, TTNT (aHR 0.84, 0.61-1.18)), and reached significance for some models (2+ ECOG TTD (aHR 0.66, 0.48-0.91)). Conclusions: First-line E-cont. regimens consistently showed increased effectiveness in outcomes compared to A-cont. regimens in mCRPC patients treated in community oncology setting. The effects sizes are modest and did not reach significance, however analysis of the sickest patients showed a trend of consistently larger effect sizes which reached significance for some outcomes. More work needs to be done to evaluate if these results support findings from other RWD sources.
Study EV-104: Phase 1 study of intravesical enfortumab vedotin for treatment of patients with non-muscle invasive bladder cancer (NMIBC)—Trial in progress.
Authors: Ashish M. Kamat, Gary D. Steinberg, Brant Allen Inman, Max R. Kates, Edward M. Uchio, Sima P. Porten, Morgan Roupret, Joan Redorta, James W.F. Catto, Girish S. Kulkarni, Thomas Powles, Mark Tyson, Gabriel P. Haas, Yao Yu, Matthew Birrenkott, Yair Lotan
Journal: Journal of Clinical Oncology (2023)

TPS582 Background: The majority of patients with bladder cancer present with non-muscle invasive disease (Chang 2016; Woldu 2017; Kates 2020; Li 2020). The standard of care for treatment of high risk NMIBC involves transurethral resection of the bladder tumor (TURBT) followed by intravesical Bacillus Calmette-Guerin (BCG) or chemotherapy. Although the response rate to BCG therapy is high, many patients recur within 1–5 years (Matulay JU 2021). For patients who have BCG unresponsive disease after adequate course of BCG, there are limited options. While radical cystectomy (RC) is still considered the standard of care, most patients are reluctant to undergo RC and their options are limited to intravesical chemotherapy or pembrolizumab. Enfortumab vedotin (EV) is an antibody-drug conjugate directed to Nectin-4, which is highly expressed in bladder tumors. In EV-301, a phase 3 study, EV showed an OS benefit vs chemotherapy in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) who had previously received platinum-based therapy and a PD-1 or PD-L1 inhibitor (Powles NEJM 2021). Based on its demonstrated benefit in la/mUC, EV is currently being evaluated in earlier UC settings. The purpose of this study is to investigate the intravesical administration of EV for patients with NMIBC. Methods: EV-104 (NCT05014139) is a phase 1, open-label, multicenter, dose-escalation and dose-expansion study designed to evaluate the safety, tolerability, PK, and antitumor activity of intravesical EV in adults with high-risk BCG-unresponsive NMIBC (carcinoma in situ with or without papillary disease) who are ineligible for or refuse RC. The dose escalation part of the trial aims to identify the maximum tolerated dose (MTD) and/or recommended dose of intravesical EV. The dose expansion part will evaluate patients at the MTD or recommended dose and further characterize safety and antitumor activity of intravesical EV. The study treatment regimen will include an induction phase, where patients will receive intravesical EV weekly for 6 weeks followed by monthly maintenance for a total of 9 additional EV doses. Patients will be assessed for response every 3 months by cystoscopy and urine cytology, while on study. Safety and antitumor activity endpoints will be summarized using descriptive statistics. The study is currently enrolling in the US with additional sites planned in Canada and the EU. Clinical trial information: NCT05014139 .
Underutilization of best systemic therapy in patients with metastatic prostate cancer.
Authors: Daniel Roadman, David Cao, Srinivas Vourganti
Journal: Journal of Clinical Oncology (2023)

111 Background: Advancement of treatment pathways in the management of metastatic prostate cancer (mPC) has identified newer systemic agents associated with survival advantage over androgen deprivation therapy (ADT) alone. Despite FDA approvals and guideline recommendations outlining standard of care (SOC) intensification of (ADT) with such additional systemic therapies such as docetaxel or novel hormonal therapies (NHT), these treatments are not being utilized uniformly by all practitioners. Our objective is to assess the utilization of such advanced therapies in patients with mPC and study differences in prescribing patterns. Methods: Between 2017 to present, we retrospectively identified all consecutive men with prostate cancer in a single health system. Electronic health record ICD code inquiries were used to identify patients. The population was further restricted utilizing diagnosis codes to include only those with metastatic prostate cancer and to exclude patients with second primary cancers. All treatment modalities and demographic information were analyzed to assess for prescribing patterns. Results: In total, 5,761 men had a diagnosis of prostate cancer. Exclusion criteria applied stepwise removed those with age &lt;18 years (2 patients) and secondary malignancies (1046 patients), resulting in 4,713 men for analysis. Of these, 665 men were found to have mPC and included in the final cohort. Mean patient age was 70.3 ± 9.6 years. We found no statistically significant difference in SOC prescribing pattern based on race, ethnicity, insurance type, zip code, 2020 United States census household median income, nor year of treatment. There was, however, overall low utilization of intensification of ADT with docetaxel or NHT at 42%, with 58% of patients still being treated with only first generation antiandrogens or luteinizing hormone releasing hormone agonists. Conclusions: In a large health system, we found that next generation care can be provided independent of insurance payor profile, race, ethnicity, and socioeconomic status. However, despite guidelines to support newer systemic agents for patients with mPC, we continue to observe that it is underused in clinical practice. Additional studies are needed to identify potential clinician and patient barriers, as well as prescribing pattern failures that are limiting the implementation of evidence-based treatment beneficial to overall survival.
Characteristics and outcomes of T1a renal cell carcinoma presenting with metastasis.
Authors: Luke Wang, Dhruv Puri, Franklin Liu, Sohail Dhanji, Margaret F Meagher, Aastha Shah, Saeed Ghassemzadeh, Juan Javier-Desloges, Aditya Bagrodia, Brent Shane Rose, James Don Murphy, Ithaar H Derweesh, Rana R. McKay
Journal: Journal of Clinical Oncology (2023)

734 Background: T1a renal cell carcinoma (RCC) is associated with excellent cure rates. However, a small fraction present with metastasis. We sought to determine the clinical characteristics, variables associated with synchronous metastasis, and survival outcomes in patients with pT1a and cT1a RCC using the National Cancer Database (NCDB). We secondarily evaluated whether surgery impacted risk of all cause mortality in cT1a RCC with synchronous lung and bone metastasis. Methods: From 2004 to 2019, all cases of RCC in patients age ≥18 were extracted from NCDB. pT1a and cT1a RCC were characterized as those 1) with no metastasis at diagnosis, 2) with synchronous metastasis [pT1aNxM1 at diagnosis]. Impact of surgery on all cause mortality was not evaluated for cT1a with synchronous metastasis to liver and brain due to low sample sizes. Results: The table describes selected characteristics of the cohorts. On multivariable logistic regression, diagnosis of pT1a with synchronous metastasis was associated with age (OR 1.02), male sex (OR 1.64), tumor size (OR 1.84), cN1 (OR 1.08), sarcomatoid (OR 5.50), tumor grade (OR 2.84) (p&lt;0.005 for these variables); and inversely with diagnosis in 2016-2019 (OR 0.66, p=0.044) and papillary histology (OR 0.45, p&lt;0.001). On multivariable Cox regression of the cT1a cohort, ACM was associated with Charlson score (HR 1.50, p&lt;0.001), metastasis to &gt;1 site (HR 2.48, p=0.032), and inversely with radical (HR 0.42, p&lt;0.001) and partial nephrectomy (HR 0.31, p&lt;0.001). In cT1a with lung metastasis, partial (HR 0.06, p=0.049) and radical nephrectomy (HR 0.17, p=0.006) was inversely associated with ACM, while surgery of distant site was not. In cT1a with bone metastasis, partial (HR 0.21, p&lt;0.001) and radical nephrectomy (HR 0.32, p&lt;0.001) were the only variables inversely associated with ACM. 5-year overall survival for pT1a with synchronous metastasis is 39.4%; for cT1a with synchronous metastasis is 20.9%. Conclusions: Known prognostic features were associated with synchronous metastasis in T1a RCC. Surgical resection of primary site may impact risk of all cause mortality in select cases of synchronous metastatic disease. [Table: see text]
COVID-19 vaccination behavior and outcomes in patients with genitourinary cancer in comparison with other cancer types.
Authors: Hyma Vani Polimera, Lauren Danielle Pomerantz, Emma Guare, Junjia Zhu, Monika Joshi
Journal: Journal of Clinical Oncology (2023)

134 Background: Cancer(ca) and old age are risk factors for developing severe COVID-19 (C19+) disease, related morbidity and mortality. These patients (pts) were excluded from clinical trials evaluating the safety and efficacy of 3 FDA approved C19 vaccines (vax). Genitourinary (GU) ca-prostate, bladder and kidney ca contribute to the majority of non-skin ca and median age of these pts range from 65-75 yrs. We aimed to study these highly vulnerable pts behavior and outcomes regarding C19 vax in comparison to non-GU ca pts (18-89 years). Methods: A prospective and observational single center study. Adult ca pts seen in clinics from Nov 2021-Sept 2022 were randomly interviewed using telephone surveys after a verbal consent. Type of ca and therapy data were collected from pts’ medical records. The survey included C19 disease status, vax status positive (+) or negative (-), reason for vax status, side effects (s.e), impact on ca Rx or ca progression. Data was entered on REDCap. The primary end point was rate of vaccination in adult ca pts. Secondary end points were to quantify C19 vax acceptance vs. hesitance, identify s.e of C19 vax and effect of C19 vax on outcomes in GU and non-GU Ca pts. Results: N=172; GU ca 21 (12.2%) and non-GU ca 151 (87.8%). Among GU ca pts- 9 had prostate ca, 7 had bladder ca and 5 had renal ca. C19+ in 4 (19%) GU and 45 (30.2%) non-GU pts. GU pts: 90.5% received C19 vax (Pfizer 47.6%; Moderna 42.9%, J &amp; J 0%); 9.5% were not vaxed. Non-GU pts: 85.2% received C19 vax (Pfizer 39.1%; Moderna 43%, J &amp; J 2.6%); 14.8% were not vaxed. The top 3 risk factors for serious C19+ were age &gt;65yr (76.2%), heart disease (61.9%) and BMI&gt;30 (42.9%) in GU ca pts and age &gt;65yr (46.4%), BMI&gt;30 (35.1%) and smoking (19.9%) in non-GU ca pts. The top 3 reasons for C19 vax (+) in GU ca pts: protection against C19+ for self (81%), for others (47.6%) and provider recommendation (38.1%). The main reasons for vax hesitancy in C19 vax (-) GU ca pts: concern for allergy to the vax (4.8%) and prior C19 infection (4.8%). The common s.e of C19 vax reported in GU ca pts were injection site inflammation (19%), headache (4.8%), muscle/body aches (4.8%) but no lymphadenopathy. None of GU ca pts reported delay in Rx or progression of the disease due to C-19 vax. Conclusions: C19 vax were overall well tolerated and did not impact ca outcomes in pts with GU malignancies. Oncologists should discuss the importance of C19 vax in the context of ca. Clinical trial information: NCT04953065 . [Table: see text]
The impact of focal therapy tumor boards, including prostate magnetic resonance imaging overreads, in refining the selection candidacy for focal therapy patients: A prospective study.
Authors: Tarik Benidir, Zaeem M Lone, Andrew Wood, Nour Abdallah, Jane Nguyen, Jihad Kaouk, Robert Stein, Samuel Haywood, Robert Abouassaly, Nima Almassi, Christopher J. Weight, Ruben Olivares, Andrei Purysko
Journal: Journal of Clinical Oncology (2023)

324 Background: Focal therapy (FT) for prostate cancer is increasingly recognized as an adequate therapeutic option in well selected men. Nevertheless, in-field and out-of-field recurrences at one year from treatment are notable. A multidisciplinary tumor board geared towards improving focal therapy (FTTB) patient selection is a novel concept which has not been explored. The impact of conducting prostate MRI-overreads during FTTB may also help refine FT candidacy and potentially reduce failure rates. We aimed to explore the value of a dedicated FTTB. Therein, we also evaluated the impact of prostate MRI overreads and its overall influence on FT candidacy. Methods: Single center, prospective study, incorporating a multidisciplinary bi-weekly FTTB (2021-2022) on patients being considered for FT. All prostate MRIs were re-reviewed by a single GU radiologist with &gt;10 years prostate MR imaging experience. Outside pathology, when requested, was also re-reviewed. The impact of such tumor boards, and specifically MRI overreads on patient candidacy are presented. Results: Forty-five patients were presented at our FTTB over the span of one year. Patient demographics are presented. Thirty-nine patients were treatment naïve while six had prior radiation +/- ADT. MRI overread was performed on all treatment naïve patients (39/45, 87%) while pathology overreads on 11/45 (24.4%) Four patients were excluded upfront due to not meeting safety criteria for FT (Urolift device (n=1), J-pouch (n=1), suspicions of metastasis at time of consideration (n=2). Among those with MRI overreads 44.7% (17/39) were found to have findings that negatively impacted eligibility for FT like lesion crossing anteriorly to the urethra occurred in (9/17), multifocal disease (8/17), discordance of lesion on prior MRI (3/17) and lesion abutting rectal wall (1/17). Pathology re-review changed management for 3/11 patients with 2/3 being downgraded to GG1 disease and opting for active surveillance. Following multidisciplinary tumor boards, twelve patients (26.7%) were deemed candidates for FT. Conclusions: FTTB increases the selection scrutiny for FT candidates. MRI overreads are a meaningful part of FT tumor boards and can change candidacy based on new or meaningful findings. FTTB with prostate MR overreads should be considered as part of the selection process in FT decision making. [Table: see text]
Gender specific differences in health-related quality of life for patients with bladder cancer following radical cystectomy.
Authors: Thilo Westhofen, Alexander Buchner, Boris Schlenker, Armin Becker, Christian G. Stief, Alexander Kretschmer
Journal: Journal of Clinical Oncology (2023)

437 Background: Previous studies have shown pronounced gender specific differences regarding diagnosis and oncological outcome for patients with bladder cancer (BC). Current literature lacks evidence on gender specific differences in health-related quality of life (HRQOL) outcomes for patients with BC following radical cystectomy (RC). We aimed to assess those gender specific differences by providing HRQOL data from a large prospective propensity score-matched cohort of patients undergoing RC with a systematic follow-up of up to 10 yrs. Methods: 1498 consecutive patients [n=421 women, n=1077 men] who underwent RC at a large tertiary care center were included. A propensity-score matched analysis of 794 patients [n=397 women, n=397 men] was conducted applying the matching- variables “patient age”, “BMI”, “pT-stage” and “type of urinary diversion”. Exclusion criteria encompassed age &lt;30 yr and RC due to benign diseases. HRQOL was assessed preoperatively, at 3 mo, then annually until a maximum follow-up of 120 months applying the validated EORTC QLQ-C30- as well as the bladder cancer-specific QLQ-BLM30- and FACT-BL-questionnaires. Separate modeling of longitudinal HRQOL for women and men was performed. Spearman’s rank correlation was applied to identify gender specific factors influencing HRQOL. Results: At baseline women and men showed no significant difference in general HRQOL assessed by the global health status domain (GHS) (p=.162). Women presented with worse mean emotional (p=.001) and cognitive (p=.007) functioning subscale. In the longitudinal analysis, a similar natural course of the GHS for women and men could be observed up to 36mo after RC (p-range: .107 - .856). Between 48mo and 96mo after RC, general HRQOL was significantly higher for men compared to women (p-range: .002-.045). At 12month a significant correlation between physical functioning or urinary continence and increased general HRQOL could equally be observed for men and women (each p&lt; .05). No significant correlation was found between sexual functioning and increased general HRQOL. While a strong correlation between Social/Family wellbeing and increased general HRQOL was found for women (p=.001), no correlation was found for men (p=.103). Conclusions: The current study provides prospective data from a unique propensity score-matched contemporary patient cohort, which displays gender specific differences in the natural course of general HRQOL and its subdomains. Those data are important to guide gender specific treatment decision-making for patients with BC.
Urologic oncology and critical care: What are prognostic factors that correlate with 6-month mortality in patients (pts) with urological tumors referred to intensive care unit (ICU)?
Authors: Giulia Kodja Zanetta, Antonio Paulo Nassar Jr, Aldo A. Dettino
Journal: Journal of Clinical Oncology (2023)

91 Background: Defining which oncologic pts actually benefit from ICU admission can be a difficult task. There is a lack of data that consistently support indication and benefit with impact on patient survival when this care is offered. The present retrospective study sought to evaluate prognostic factors related to mortality in 6 months after hospital discharge of pts with urological tumors admitted to ICU at the A C Camargo Cancer Center. Methods: A retrospective cohort study of pts with urological cancers (bladder, prostate, kidney, testicular, and other) admitted to ICU in 2017-2018. We collected the following data to identify possible predictors of 6-month mortality: gender, age, Eastern Cooperative Oncology Group (ECOG) performance status, type of ICU admission (planned or unplanned), clinical stage at diagnosis (locoregional vs. metastatic). All these variables were included in a logistic regression model with mortality at 6 months as the dependent variable. Results: Assessing the medical record of 677 patients, the pts with ECOG grading &gt;2 presented poorer results compared to the ones 0-2, with an Odds Ratio (OR) 5.10 [Confidence Interval 95% (CI) 2.46-11.69]. The urological tumor type did influence the 6-month mortality, with the best results for pts with testicular tumors: OR 0.27 (CI 0.05-0.99) and the worst ones to bladder tumors with an OR 2.35 (CI 1.44-3.87) when compared to prostate tumors. For metastatic diagnoses, as expected, the mortality results appeared to be worse than for pts with locoregional disease, with an OR 4.06 (CI 2.73-6.07). Finally, pts undergoing unplanned hospitalization at ICU, understanding clinical and surgical ones, presented poorer results compared to the elective ones, with an OR 3.22 (2.16-4.84). Conclusions: In this cohort of pts with urological cancers, 6-month mortality was 39%. Performance status, bladder cancer, metastatic disease and unplanned hospitalizations were all associated with increased mortality.